Abstract
Coiled coils are characterized by an arrangement of two or more α-helices into a superhelix and one of few protein motifs where the sequence-to-structure relationship to a large extent have been decoded and understood. The abundance of both natural and de novo designed coil coils provides a rich molecular toolbox for self-assembly of elaborate bespoke molecular architectures, nanostructures, and materials. Leveraging on the numerous possibilities to tune both affinities and preferences for polypeptide oligomerization, coiled coils offer unique possibilities to design modular and dynamic assemblies that can respond in a predictable manner to biomolecular interactions and subtle physicochemical cues. In this review, strategies to use coiled coils in design of novel therapeutics and advanced drug delivery systems are discussed. The applications of coiled coils for generating drug carriers and vaccines, and various aspects of using coiled coils for controlling and triggering drug release, and for improving drug targeting and drug uptake are described. The plethora of innovative coiled coil-based molecular systems provide new knowledge and techniques for improving efficacy of existing drugs and can facilitate development of novel therapeutic strategies.
Highlights
Coiled coils are abundant structural motifs found in many fibrous proteins and transcription factors and are often involved in assembly of higher order protein structures [1]
The knowledge generated from systematic investigations of the roles of individual amino acids on folding and oligomerization in both natural proteins and synthetic peptides have facilitated de novo design of numerous different polypeptides that form well-defined coiled coils under various conditions [6,7,8]
Tests in vitro and in vivo showed that Pt (IV)-RCHH could induce apoptosis of GB cells at a five-fold lower Pt (IV) concentration that the pro-drug alone while showing no effects on astrocytes [102]. In another attempt to combine coiled coils with elastin like protein (ELP), Park and Champion demonstrated the possibility to assemble vesicle-like structures using recombinant arginine-rich (ZR) and glutamic acid-rich (ZE) leucine zipper motifs fused with an ELP motif or a globular protein, respectively (Fig. 7)
Summary
Coiled coils are abundant structural motifs found in many fibrous proteins and transcription factors and are often involved in assembly of higher order protein structures [1]. A large number of coiled coils with various preferences and affinities for oligomerization have been developed and a wealth of natural coiled coil sequences have been explored This has in turn enabled engineering of an amazing repertoire of higherorder coiled coil supramolecular assemblies, such as fibers [9,10,11], hydrogels [12,13,14,15,16,17,18], and structurally defined discrete nanostructures [19,20]. We cover all these areas and highlight and discuss recent work on applications of coiled coils in design of novel therapeutic strategies and advanced drug delivery applications
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